Studies on the mechanisms of the host range determination of lentiviruses from carnivora

人类免疫缺陷病毒（HIV）属于慢病毒属，并在人类中诱导免疫缺陷。动物也有自己的慢病毒，并导致各种疾病。猫也有一种叫做猫免疫缺陷病毒（FIV）的致病性慢病毒，FIV在大鼠中诱导免疫缺陷，类似于人类的HIV感染。大型猫科动物如狮子也有慢病毒，但这些病毒在自然宿主中是非致病性的。阐明猫慢病毒宿主范围的确定机制，对于应对猫类慢病毒感染的出现具有重要意义。我们分析了FIV感染猫神经胶质细胞系G355 - 5细胞的机制。FIV毒株Petaluma（A亚型）感染G355 - 5细胞，与猫CD 134（fCD 134）（T淋巴细胞FIV的主要受体）的表达无关。另一方面，菌株TM 2（亚型B）需要fCD 134的异位表达来感染G355 - 5细胞。有趣的是，offCD 134的强表达抑制了G355 - 5细胞中Petaluma菌株的感染。此外，fCD 134的表达抑制了菌株TM 2从感染的G855 - 5细胞的有效病毒释放。用fCD 134转导的菌株TM2感染的G355 - 5细胞（G355 - 5/f0X40细胞）变为持续感染状态。在感染后50天，感染的细胞将感染性FIV颗粒释放到培养基中，病毒被命名为菌株TM2PI。TM2PI在fCD 134不存在下感染初始G355 - 5细胞，表明菌株TM2在G355 - 5细胞中突变为fCD 134非依赖性菌株。此外，细胞也变成持续感染的状态，并且可以在不与未感染的G355 - 5细胞共培养的情况下维持。由于病毒和生产细胞均未通过基因工程技术进行修饰，因此生产细胞可能适用于疫苗用病毒的抗原制备。

Human immunodeficiency virus (HIV) belongs to the genus lentivirus and induces immunodeficiency in humans. Animals also have own lentiviruses and cause a variety of diseases. Cats also have a pathogenic lentivirus called feline immunodeficiency virus (FIV) and FIV induces immunodeficiency in rats similar to the HIV infection in humans. Large felids such as lions also have lentiviruses, however the viruses are non-pathogenic in natural hosts. To elucidate the mechanisms on the determination of the host range of the feline lentiviruses is important to cope with the emergence of the novel lentiviral infections in felids. We analyzed the mechanisms of FIV infection in a feline glial cell line termed G355-5 cells. FIV strain Petaluma (subtype A) infected the G355-5 cells irrespective of the expression of feline CD134 (fCD134), primary receptor for T-lymphotropic FIV. On the other hand, strain TM2 (subtype B) required the ectopic expression of fCD134 to infect the G355-5 cells. Intriguingly, the strong expression of offCD134 suppressed the infection by strain Petaluma in the G355-5 cells. In addition, the expression of fCD134 suppressed the efficient viral release of strain TM2 from the infected G855-5 cells. The strain TM2-infected G355-5 cells transduced with fCD134 (G355-5/fOX40 cells) became a state of persistent infection. At 50 days post-infection, the infected cells released the infectious FIV particles into the culture medium and the virus was designated as strain TM2PI. TM2PI infected naive G355-5 cells in the absence of fCD134, indicating that strain TM2 mutated in the G355-5 cells to be an fCD134-independent strain. Furthermore, the cells also became a state of persistent infection and can be maintained without coculturing with uninfected G355-5 cells. Because both virus and producer cells were not modified by the genetic engineering techniques, the producer cells may be suitable for antigen preparation of the virus for vaccines.